source: Neuromuscular Disorders
E. Henricson, C. McDonald, A. Mayhew, A. Bagley, N. Joyce, B. Oskarsson, L. Sodeberg-Miller, S. Liu, R. Abresch, CINRG Investigators
Person-reported outcome (PRO) measures for DMD clinical trials should be tied to meaningful disease milestones such as loss of ability to stand, rise from a chair, climb stairs, walk independently, raise a hand to the mouth, as well as need for non-invasive ventilation. We developed the DMD lifetime mobility scale (DMD-LMS) with data from the CINRG Duchenne natural history study, using mobility items from the PODCI, PedsQL, PedsQL NMM, pediatric and adult mobility scales of the NeuroQOL. “Successful” question items: a) differentiated between milestone groups; b) showed significant change over one-year, and c) were deemed “clinically significant” by exceeding change of 1/3 the standard deviation of the measure. We conducted Rasch analyses of successful question sets classified by WHO-ICF mobility subdomains (Walking and Moving, Changing and Maintaining Body Position, Carrying, Moving and Handling Objects) to evaluate their clinical validity, targeting, dependency, model fit and person-separation across the full range of observed DMD mobility. Four hundred and ten participants (age at initial visit 11.3[5.7] years, range 4 – 28) completed surveys and clinical testing with follow-up up to month 96 (3066 completed visits). Rasch analysis-based refinement of the question set yielded a continuously scored mobility scale representing lower extremity, trunk, and upper extremity function that differentiates between disease milestones across the current DMD lifespan. We evaluated question item coverage versus the NSAA, EK Scale and PUL Assessment to identify additional questions to address gaps, ceiling and floor effects in the draft scales. Field testing of the DMD-LMS is ongoing. The DMD-LMS is a draft PRO instrument constructed using modern psychometric methods that represents the full range of mobility in DMD, maps directly to items in clinical measures of function, and is responsive disease progression over one year.
University of California, USA; Newcastly University, UK; Shriner’s Hospital Northern California, USA; Mayo Clinic, USA; University of California, USA; Cooperative International Neuromuscular Research Group, Washington, USA